rs148619105

Positions:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

This summary comes from the ClinGen Evidence Repository: The c.4004G>A (p.Gly1335Glu) variant in TECTA gene has been detected in heterozygosity in 1 individual with sloping moderately-severe sensorineural hearing loss but no variant on the other allele was identified (Partners LMM internal data). The filtering allele frequency of the variant in the TECTA gene is 0.358% for African chromosomes in gnomAD (89/24844 with 95% CI), which is a high enough frequency to be classified as likely benign based on the thresholds defined by the ClinGen Hearing Loss Expert Panel (HL EP) for autosomal recessive hearing loss variants (BS1). In summary, the HL EP classified this variant as likely benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BS1. LINK:https://erepo.genome.network/evrepo/ui/classification/CA6327326/MONDO:0019497/005

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

TECTA
NM_005422.4 missense

Scores

Clinical Significance

Likely benign reviewed by expert panel U:2B:3

Conservation

PhyloP100: 5.22

Variant links:

Genes affected

TECTA (HGNC:11720): (tectorin alpha) The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals. Alpha-tectorin is one of the major noncollagenous components of the tectorial membrane. Mutations in the TECTA gene have been shown to be responsible for autosomal dominant nonsyndromic hearing impairment and a recessive form of sensorineural pre-lingual non-syndromic deafness. [provided by RefSeq, Jul 2008]

TECTA links:

TBCEL-TECTA (HGNC:54857): (TBCEL-TECTA readthrough) Predicted to enable alpha-tubulin binding activity. Predicted to be involved in microtubule cytoskeleton organization; post-chaperonin tubulin folding pathway; and tubulin complex assembly. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TBCEL-TECTA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECTA	NM_005422.4 link	c.4004G>A	p.Gly1335Glu	missense_variant	12/24	ENST00000392793.6	NP_005413.2	O75443
TBCEL-TECTA	NM_001378761.1 link	c.4961G>A	p.Gly1654Glu	missense_variant	18/30		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6 link	c.4004G>A	p.Gly1335Glu	missense_variant	12/24	5	NM_005422.4	ENSP00000376543.1		O75443

Frequencies

GnomAD3 genomes

AF:

0.00100

AC:

153

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00335

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000243

AC:

AN:

250702

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.00329

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000889

AC:

130

AN:

1461740

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00302

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.00100

AC:

153

AN:

152360

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00334

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000234

Hom.:

Bravo

AF:

0.00130

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000321

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:2Benign:3

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not provided

Uncertain:2Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 03, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 11, 2023	- -
Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Feb 08, 2022	Located in the zona adhesion region (Hildebrand et al., 2011); Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Sep 22, 2016

p.Gly1335Glu in exon 11 of TECTA: This variant is not expected to have clinical significance because it has been identified in 0.3% (38/10052) of African chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs148619105). -

Nonsyndromic genetic hearing loss

Benign:1

Likely benign, reviewed by expert panel

curation

ClinGen Hearing Loss Variant Curation Expert Panel

Apr 08, 2021

The c.4004G>A (p.Gly1335Glu) variant in TECTA gene has been detected in heterozygosity in 1 individual with sloping moderately-severe sensorineural hearing loss but no variant on the other allele was identified (Partners LMM internal data). The filtering allele frequency of the variant in the TECTA gene is 0.358% for African chromosomes in gnomAD (89/24844 with 95% CI), which is a high enough frequency to be classified as likely benign based on the thresholds defined by the ClinGen Hearing Loss Expert Panel (HL EP) for autosomal recessive hearing loss variants (BS1). In summary, the HL EP classified this variant as likely benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BS1. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;.;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.91

.;D;D

M_CAP

Benign

0.051

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.2

L;.;L

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.7

D;.;D

REVEL

Uncertain

0.35

Sift

Benign

0.037

D;.;D

Sift4G

Benign

0.36

T;.;T

Polyphen

0.70

P;.;P

Vest4

0.32

MVP

0.90

MPC

0.85

ClinPred

0.049

GERP RS

5.0

Varity_R

0.38

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over